The present invention relates to atmospheric pressure ionization ion mobility spectrometry, for example electrospray ionization ion mobility spectrometry, and more particularly to an improved spectrometer and method for throughput sample screening under ambient conditions.
Among the current trends in separation science is reduction of analysis time. Traditional separation methods lose separation quality, in terms of efficiency and resolution, as analysis times are shortened. Conditions adopted for achieving fast separations in liquid chromatography or capillary electrophoresis, such as high pressures and/or electric potentials, can be costly, potentially dangerous and/or can decrease the lifetime of the instrumentation. In addition, compounds which can be separated in minutes can be difficult or impossible to separate more quickly by altering conditions such as mobile phase linear velocity rate or analytical column length. Yet, despite the potential problems, performing fast separations can be very attractive in certain applications. Decreased resolution and separation efficiency may not be detrimental to the analysis, depending on what information is required. If the primary goal is to identify the presence or absence of certain compounds in a simple mixture, a quick screening method may be all that is needed, and a fast separation would be preferred. However, if a complete qualitative and quantitative analysis of all compounds within a mixture is needed, a fast separation may lack the ability to supply all of the necessary information. However, the requirement for thorough analysis may not be known until after a quick screening is performed.
Ion mobility spectrometry (IMS) is a form of gas-phase electrophoresis in which ions are separated based on their mobilities through a drift tube under constant electric potential. Ion mobility is dependent on factors including ion size, charge, and shape. Typically, ions are created at atmospheric pressure and gated through a drift tube against a counter flow of inert drift gas such as air, helium, or nitrogen. Separations occur within milliseconds. Gates are placed at the entrance (and sometimes the exit) of the drift tube and are systematically opened and closed to permit ions to pass through the instrument in such a fashion as to allow desired data to be collected.
Although initially introduced as plasma chromatography, ion mobility spectrometry has been used primarily as a stand-alone detector and has not traditionally been considered to be a useful technique for separating ions due to its relatively low resolution and separation efficiency. IMS performance was not generally considered in terms of chromatographic figures of merit. This may have been, in part, due to the fact that analyses were performed at speeds more representative of detectors rather than conventional separators. In addition, primitive IMS had very poor separation efficiency. Recently, reported efficiencies have improved considerably. These high efficiencies were achieved due to improvements to IMS design, increased electric field homogeneity and detection speed, decreased sample size and gate pulse width and, in some cases, by applying the technique to the analysis of large biomolecules in which electrospray ionization produces multiply charged ions. Recently reported high efficiencies make modern IMS an attractive alternative to other fast separation techniques.
Traditionally, IMS has used radioactive material as an ionizing source. Unfortunately, solely gas-phase compounds could be ionized. U.S. Pat. No. 4,390,784 to Browning et al. discloses an ion mobility detector cell having a reactant region within which gaseous ions are ionized from a gaseous sample and from which ions are injected into a drift tube. An accelerating field is provided by a ceramic tube with a resistive film coating across which a voltage is applied.
Atmospheric pressure ionization (API), including atmospheric pressure chemical ionization (APCI) and electrospray ionization can serve as a source of ions. Only recently has electrospray ionization been adapted to IMS. This has allowed the analysis of liquid samples that contain compounds ranging from low molecular weight to large biomolecules. The principal obstacles to be overcome were, first, the analyte had to be desolvated prior to entrance into the IMS drift tube and, second, a means for keeping the large amounts of solvent being electrosprayed, particularly water, from entering the IMS had to be devised. It has been proposed that these problems be surmounted by the use of a heated or a reduced depressurized desolvation region. APCI also involves the use of solvents and presents similar problems.
U.S. Pat. No. 5,905,258 to Clemmer et al. discloses an ion mobility spectrometer having a drift tube contained in a temperature controlled chamber containing pressurized static buffer gas. Ions are admitted to the drift tube from an ion source wherein a laser is used to desorb gaseous ions from the surface of a sample.
Guevremont et al., xe2x80x9cCombined Ion Mobility/Time of Flight Mass Spectometry Study of Electrospray-Generated Ionsxe2x80x9d, Anal. Chem. Vol. 69, No. 19, Oct. 1, 1997, describes an ion mobility spectrometer with an electrospray ion source supplying ions from a chamber through a transfer line to a drift region. A gas stream entering the transfer line is divided, with part entering the drift region, in an attempt to reduce the amount of solvent entering the drift region.
Srebalus et al., xe2x80x9cGas-Phase Separations of Electrosprayed Peptide Librariesxe2x80x9d, Anal. Chem. Vol. 71, No. 18, Sep. 15, 1999, describes an ion mobility spectrometer in which ions are electrosprayed at atmospheric pressures into a differentially pumped reduced pressure desolvation region and are moved by an electric field through an opposing stream of pumped buffer gas from the desolvation region into a drift tube. The desolvation region includes a series of conductive lenses interconnected by resistors and separated by insulating spacers.
There is a need for an API IMS operable under ambient conditions, for a number of reasons. First, ion mobility spectrometers have been used quite successfully as field-portable instruments due to their robustness, small size, minimal power consumption, and simple means of operation. But with the addition of large heaters or roughing pumps to desolvate electrosprayed ions and to keep the drift tube free of solvent, a degree of portability is lost. Second, in comparison, an IMS that can be operated under ambient conditions is initially less costly and thereafter easier to maintain. Third, heat labile compounds can be analyzed, while a rigorously heated desolvation region limits the analysis of such compounds.
A principal object of the present invention is to provide an improved ion mobility spectrometry instrument operable for high throughput screening under ambient conditions. Other objects are to provide an API ion mobility spectrometer able to achieve reliable and effective desolvation without special heat or pressure capabilities or complex drift gas ducting; to provide improved API ion mobility spectrometry methods; to provide an API ion mobility spectrometer that is simple and inexpensive relative to known devices without sacrificing performance; and to provide ion mobility spectrometry apparatus and methods overcoming shortcomings of known devices and methods.
In brief, in accordance with the invention there is provided an ion mobility spectrometer including a source of ions and solvent and a desolvation region receiving ions and solvent from the source. A drift tube has an ion inlet end and an ion outlet end. An ion transfer portal is located between the desolvation region and the drift tube inlet end. An ion propulsion field is applied along the drift tube. A drift gas inlet is adjacent the drift tube outlet end and a drift gas outlet is in the desolvation region. The ion transfer portal includes a wall separating the desolvation region from the drift tube, and an aperture in the wall providing a restricted drift gas flow path from the drift tube to the desolvation region.